[Effect of mutation-induced excess brain concentration of intermediates of the kynurenine pathway of tryptophan metabolism on stress resistance and courtship behavior and communicative sound production in male Drosophila melanogaster].

The resistance of courtship behavior and communicative sound production to heat shock (37 degrees C, 30 min) was studied in wild-type Canton S (CS) male Drosophila melanogaster and males of two strains with defects in the kynurenine pathway of tryptophan metabolism (KPTM) caused by mutations cinnabar (block at the level of kynurenine-3-hydroxylase leading to accumulation of kynurenic acid, a neuroprotective metabolite, in the brain) and cardinal (block at the level of phenoxazinone synthetase causing accumulation of 3-hydroxykynurenine, an oxidative stress generator, in the brain). Males of each strain were divided into four groups. Males from control groups were not exposed to heat shock. The other groups were exposed to heat shock at the late embryonic/early larval (the first instar) developmental stage, when mushroom bodies are formed (HS1 groups); at the prepupal stage, when the brain central complex develops (HS2 groups); or at the imago stage 1 h before the experiment (HS groups). All males were tested at an age of five days. Virgin and fertilized five-day-old CS females served as courtship objects. The courtship behavior and singing of control CS and cinnabar males were similar. Control cardinal males also had high motivation, but their courtship efficiency was lower because of less precise movements (wing vibration was often not accompanied by sound production) and hyperexcitability. Exposure of first-instar larvae to heat shock had almost no effect on behavior or singing of adult males of any strain. In cardinal males exposed to heat shock at the prepupal stage or, especially, at the imago stage 1 h before the test (the HS2 and HS groups), courtship was strongly impaired, and various distortions appeared in their sound signals, which indicated disturbance of coordination between elements of the song center and their interaction with pacemakers. These effects were much milder or absent altogether in HS2 and HS wild-type males and, especially, cinnabar males. Thus, permanent excess of 3-hydroxykynurenine in the male brain dramatically decreased their stress resistance. In contrast, excess of kynurenic acid alleviated the consequences of stress.

The role of the flabellar and ellipsoid bodies of the central complex of the brain of Drosophila melanogaster in the control of courtship behavior and communicative sound production in males.

The role of flabellar and ellipsoid bodies of the central complex of the brain of Drosophila melanogaster males in controlling courtship behavior and the accompanying sound production was studied by comparative analysis of the characteristics of courtship and singing in wild-type flies and individuals of five mutant lines with different anatomical defects in these parts of the brain. Investigations were performed using the following fly lines: Canton S (wild-type, controls), ebo(KS263), with defects only in the ellipsoid bodies, and ebo(1041), ceb(849), ceb(892), and cba(KS96), with different levels of abnormality in both parts of the central complex. The data obtained here indicated that the flabellar and ellipsoid bodies are involved in: 1) maintaining a high level of courtship activity; 2) regulating the precision of male movements while following females; 3) in controlling the nature and stability of the sound elements from which communicative signals are constructed; 4) in regulating the rhythmic structure of signals dependent on the stability of pacemakers function; 5) establishing the relationship between behavior and the context in which it occurs.

[Architecture of the X chromosome, expression of LIM kinase 1, and recombination in the agnostic mutants of Drosophila: a model of human Williams syndrome]. / Osobennosti arkhitektury X-khromosomy, ékspressii LIM kinazy 1 i rekombinatsii u mutantov drozofily lokusa agnostic: model' sindroma uil'iamsa cheloveka.

As the Human Genome and Drosophila Genome Projects were completed, it became clear that functions of human disease-associated genes may be elucidated by studying the phenotypic expression of mutations affecting their structural or functional homologs in Drosophila. Genomic diseases were identified as a new class of human disorders. Their cause is recombination, which takes place at gene-flanking duplicons to generate chromosome aberrations such as deletions, duplications, inversions, and translocations. The resulting imbalance of the dosage of developmentally important genes arises at a frequency of 10(-3) (higher than the mutation rate of individual genes) and leads to syndromes with multiple manifestations, including cognitive defects. Genomic DNA fragments were cloned from the Drosophila melanogaster agnostic locus, whose mutations impair learning ability and memory. As a result, the locus was exactly localized in X-chromosome region 11A containing the LIM kinase 1 (LIMK1) gene (CG1848), which is conserved among many species. Hemizygosity for the LIMK1 gene, which is caused by recombination at neighboring extended repeats, underlies cognitive disorders in human Williams syndrome. LIMK1 is a component of the integrin signaling cascade, which regulates the functions of the actin cytoskeleton, synaptogenesis, and morphogenesis in the developing brain. Immunofluorescence analysis revealed LIMK1 in all subdomains of the central complex and the visual system of Drosophila melanogaster. Like in the human genome, the D. melanogaster region is flanked by numerous repeats, which were detected by molecular genetic methods and analysis of ectopic chromosome pairing. The repeats determined a higher rate of spontaneous and induced recombination. including unequal crossing over, in the agnostic gene region. Hence, the agnostic locus was considered as the first D. melanogaster model suitable for studying the genetic defect associated with Williams syndrome in human.

[The fan-shaped and ellipsoid bodies of the brain central complex are involved in the control of courtship behavior and communicative sound production in Drosophila melanogaster males]. / O roli veeroobraznogo i éllipsoidnogo tel tsentral'nogo kompleksa golovnogo mozga Drosophila melanogaster v kontrole povedeniia ukhazhivaniia samtsov.

To elucidate the role of the fan-shaped and ellipsoid bodies (FB and EB) of the central complex of Drosophila melanogaster brain in the control of male courtship behavior and singing, we analyzed characteristics of the courtship behavior and parameters of the communicative sound signals accompanying it in wild type flies and in flies from 5 mutant strains with various anatomical defects in FB and EB. The following strains of flies were used for experiments: Canton S (wild type, the control), eboKS263 with defects only in EB and ebo1041, ceb849, ceb892 and cbdKS96 with both the FB and EB damaged in different manner. The data obtained suggest that the FB and EB are involved: 1) in maintenance of a high courtship activity level, 2) in the control of accuracy of male following movements when courting a female, 3) in the control of the form and stability of sound elements in courtship songs, 4) in the control of the rhythmic structure of courtship songs determined by the stability of the pacemakers, and 5) in setting up a correspondence between the current behavior and the external situation.

Mutational analysis and genetic cloning of the agnostic locus, which regulates learning ability in Drosophila.

P-insertion mutations were obtained and localized by in situ methods at the agnostic gene (agn: 1-38.9; 11AB) in Drosophila. All agn mutants showed a wide spectrum of pleiotropic effects: an EMS-induced mutation of the agn-ts398 improved the ability to develop a conditioned defensive response and increased the activity of cAMP metabolic enzymes; spontaneous mutation of agnX1 showed morphological defects of the brain. P-insertion mutations were used to clone the gene; a restriction map of 80 kb in length was determined, and the insertion was localized to a fragment of 9 kb.

[Mutational analysis and genetic cloning of the agnostic locus controlling learning ability in Drosophila]. / Mutatsionnyi analiz i geneticheskoe klonirovanie lokusa agnostic, kontroliruiuschego sposobnost'k obucheniiu, u drozofily.

The ts-mutations of the agnostic gene either increased or decreased the activity of the AC and PDE. A chromosomal deficiency in the 11B region failed to complement with the agnostic behavioral defect like agn P29 and P40, led to an increased proportion of the PDE-1 in total PDE and to the structural defects in the central complex thus indicating that the P insertion is responsible for the mutant agnostic phenotype.